Stoics against stoics in Cudworth's "A Treatise of Freewill"

In his 'A Treatise of Freewill', Ralph Cudworth argues against Stoic determinism by drawing on what he takes to be other concepts found in Stoicism, notably the claim that some things are ‘up to us’ and that these things are the product of our choice. These concepts are central to the late Stoic Epictetus and it appears at first glance as if Cudworth is opposing late Stoic voluntarism against early Stoic determinism. This paper argues that in fact, despite his claim to be drawing on Stoic doctrine, Cudworth uses these terms with a meaning first articulated only later, by the Peripatetic commentator Alexander of Aphrodisias

Global trends in pediatric burn injuries and care capacity from the World Health Organization Global Burn Registry

BackgroundBurn injuries are a major cause of death and disability globally. The World Health Organization (WHO) launched the Global Burn Registry (GBR) to improve understanding of burn injuries worldwide, identify prevention targets, and benchmark acute care. We aimed to describe the epidemiology, risk factors, and outcomes of children with burns to demonstrate the GBR's utility and inform needs for pediatric burn prevention and treatment.MethodsWe performed descriptive analyses of children age ≤ 18 years in the WHO GBR. We also described facility-level capacity. Data were extracted in September of 2021.ResultsThere were 8,640 pediatric and adult entries from 20 countries. Of these, 3,649 (42%) were children (0–18 years old) from predominantly middle-income countries. The mean age was 5.3 years and 60% were boys. Children aged 1–5 years comprised 62% (n = 2,279) of the cohort and mainly presented with scald burns (80%), followed by flame burns (14%). Children >5 years (n = 1,219) more frequently sustained flame burns (52%) followed by scald burns (29%). More than half of pediatric patients (52%) sustained a major burn (≥15% total body surface area) and 48% received surgery for wound closure during the index hospitalization. Older children had more severe injuries and required more surgery. Despite the frequency of severe injuries, critical care capacity was reported as “limited” for 23% of pediatric patients.ConclusionsChildren represent a large proportion of people with burn injuries globally and often sustain major injuries that require critical and surgical intervention. However, critical care capacity is limited at contributing centers and should be a priority for healthcare system development to avert preventable death and disability. This analysis demonstrates that the GBR has the potential to highlight key epidemiological characteristics and hospital capacity for pediatric burn patients. To improve global burn care, addressing barriers to GBR participation in low- and low-middle-income countries would allow for greater representation from a diversity of countries, regions, and burn care facilities

New flexible protective coating for printed smart textiles

In the field of food packaging, the addition of exfoliated layered silicates in polymers has been established to improve the polymers’ gas barrier properties. Using these polymers as coatings to protect smart textiles from oxidation and corrosion while maintaining their textile properties should significantly extend their lifetime and promote their market penetration. The aim of this study was to print new polymer dispersions containing layered silicates to protect screen-printed conductive structures, and to test the resulting samples. For this, appropriate printing parameters were determined by statistical design of experiments. According to these results, conductive structures were printed and protected with the selected coating. The abrasion resistance and the continuity of the protective layer of the printed samples were then measured. A continuous protective coating of approximately 70–80 µm thickness was applied on a conductive structure. The printed samples showed a very high resistance to abrasion (unchanged by 85,000 abrasion cycles) while remaining flexible and presenting a lower water vapor permeability (<2.5 g/m² d) than the coatings commonly used in the textile field.Arbeitsgemeinschaft industrieller Forschungsvereinigunge

Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis

In addition to motor neurone degeneration, up to 50% of amyotrophic lateral sclerosis (ALS) patients present with cognitive decline. Understanding the neurobiological changes underlying these cognitive deficits is critical, as cognitively impaired patients exhibit a shorter survival time from symptom onset. Given the pathogenic role of synapse loss in other neurodegenerative diseases in which cognitive decline is apparent, such as Alzheimer's disease, we aimed to assess synaptic integrity in the ALS brain. Here, we have applied a unique combination of high-resolution imaging of post-mortem tissue with neuropathology, genetic screening and cognitive profiling of ALS cases. Analyses of more than 1 million synapses using two complimentary high-resolution techniques (electron microscopy and array tomography) revealed a loss of synapses from the prefrontal cortex of ALS patients. Importantly, synapse loss was significantly greater in cognitively impaired cases and was not due to cortical atrophy, nor associated with dementia-associated neuropathology. Interestingly, we found a trend between pTDP-43 pathology and synapse loss in the frontal cortex and discovered pTDP-43 puncta at a subset of synapses in the ALS brains. From these data, we postulate that synapse loss in the prefrontal cortex represents an underlying neurobiological substrate of cognitive decline in ALS

Alpha-synuclein prevents the formation of spherical mitochondria and apoptosis under oxidative stress

Oxidative stress (OS), mitochondrial dysfunction, and dysregulation of alpha-synuclein (aSyn) homeostasis are key pathogenic factors in Parkinson’s disease. Nevertheless, the role of aSyn in mitochondrial physiology remains elusive. Thus, we addressed the impact of aSyn specifically on mitochondrial response to OS in neural cells. We characterize a distinct type of mitochondrial fragmentation, following H(2)O(2) or 6-OHDA-induced OS, defined by spherically-shaped and hyperpolarized mitochondria, termed “mitospheres”. Mitosphere formation mechanistically depended on the fission factor Drp1, and was paralleled by reduced mitochondrial fusion. Furthermore, mitospheres were linked to a decrease in mitochondrial activity, and preceded Caspase3 activation. Even though fragmentation of dysfunctional mitochondria is considered to be a prerequisite for mitochondrial degradation, mitospheres were not degraded via Parkin-mediated mitophagy. Importantly, we provide compelling evidence that aSyn prevents mitosphere formation and reduces apoptosis under OS. In contrast, aSyn did not protect against Rotenone, which led to a different, previously described donut-shaped mitochondrial morphology. Our findings reveal a dichotomic role of aSyn in mitochondrial biology, which is linked to distinct types of stress-induced mitochondrial fragmentation. Specifically, aSyn may be part of a cellular defense mechanism preserving neural mitochondrial homeostasis in the presence of increased OS levels, while not protecting against stressors directly affecting mitochondrial function

The Role of Multidimensional Prognostic Index to Identify Hospitalized Older Adults with COVID-19 Who Can Benefit from Remdesivir Treatment: An Observational, Prospective, Multicenter Study

Background: Data regarding the importance of multidimensional frailty to guide clinical decision making for remdesivir use in older patients with coronavirus disease 2019 (COVID-19) are largely unexplored. Objective: The aim of this research was to evaluate if the Multidimensional Prognostic Index (MPI), a multidimensional frailty tool based on the Comprehensive Geriatric Assessment (CGA), may help physicians in identifying older hospitalized patients affected by COVID-19 who might benefit from the use of remdesivir. Methods: This was a multicenter, prospective study of older adults hospitalized for COVID-19 in 10 European hospitals, followed-up for 90 days after hospital discharge. A standardized CGA was performed at hospital admission and the MPI was calculated, with a final score ranging between 0 (lowest mortality risk) and 1 (highest mortality risk). We assessed survival with Cox regression, and the impact of remdesivir on mortality (overall and in hospital) with propensity score analysis, stratified by MPI = 0.50. Results: Among 496 older adults hospitalized for COVID-19 (mean age 80 years, female 59.9%), 140 (28.2% of patients) were treated with remdesivir. During the 90 days of follow-up, 175 deaths were reported, 115 in hospital. Remdesivir treatment significantly reduced the risk of overall mortality (hazard ratio [HR] 0.54, 95% confidence interval CI 0.35–0.83 in the propensity score analysis) in the sample as whole. Stratifying the population, based on MPI score, the effect was observed only in less frail participants (HR 0.47, 95% CI 0.22–0.96 in propensity score analysis), but not in frailer subjects. In-hospital mortality was not influenced by remdesivir use. Conclusions: MPI could help to identify less frail older adults hospitalized for COVID-19 who could benefit more from remdesivir treatment in terms of long-term survival

Establishment and dynamics of the balsam fir seedling bank in old forests of northeastern Quebec

This study examines balsam fir (Abies balsamea (L.) Mill.) recruitment in old fir stands. Studying the regeneration of these stands is essential to understand the regeneration dynamic of the species in the absence of standdestroying disturbances. The objectives were (1) to obtain substrate-seedling associations for different age-classes and according to the presence or absence of adventitious roots; (2) to evaluate the contribution of the seed rain to seedling recruitment; (3) to re-examine age structures using the most appropriate method that minimizes estimation errors due to the presence of adventitious roots. A total of 90 quadrats (1 m2) were established along transects. In each quadrat, subtrates were characterized (type and topography) and their area was estimated. All balsam fir seedlings (<50 cm tall) present in the quadrats were located, harvested whole (root and shoot), and described (age, height, presence of adventitious roots, etc). Fir seedlings were strongly associated with woody mounds covered with thin mats of mixed mosses and Pleurozium shreberi (Bird.) Mitt. but negatively associated with flat topography particularly dominated by Hylocomium splendens (Hedw.) B.S.G. The presence of adventitious root is related to seedling age more than substrate type or topography. The age structure is in agreement with seed production and disturbance regime

The LSD1-Type Zinc Finger Motifs of Pisum sativa LSD1 Are a Novel Nuclear Localization Signal and Interact with Importin Alpha

Background: Genetic studies of the Arabidopsis mutant lsd1 highlight the important role of LSD1 in the negative regulation of plant programmed cell death (PCD). Arabidopsis thaliana LSD1 (AtLSD1) contains three LSD1-type zinc finger motifs, which are involved in the protein-protein interaction. Methodology/Principal Findings: To further understand the function of LSD1, we have analyzed cellular localization and functional localization domains of Pisum sativa LSD1 (PsLSD1), which is a homolog of AtLSD1. Subcellular localization analysis of green fluorescent protein (GFP)-tagged PsLSD1 indicates that PsLSD1 is localized in the nucleus. Using a series of GFP-tagged PsLSD1 deletion mutants, we found that the three LSD1-type zinc finger motifs of PsLSD1 alone can target GFP to the nucleus, whereas deletion of the three zinc finger motifs or any individual zinc finger motif causes PsLSD1 to lose its nuclear localization, indicating that the three zinc finger motifs are necessary and sufficient for its nuclear localization. Moreover, site-directed mutagenesis analysis of GFP-tagged PsLSD1 indicates that tertiary structure and basic amino acids of each zinc finger motif are necessary for PsLSD1 nuclear localization. In addition, yeast two-hybrid, pull-down, and BiFC assays demonstrate that the three zinc finger motifs of PsLSD1 directly bind to importin alpha in vitro and in vivo. Conclusions/Significance: Our data demonstrate that the LSD1-type zinc finger motifs of PsLSD1 are a novel nuclear localization signal and directly bind to importin alpha, and suggest that the nuclear import of LSD1 may rely on the interaction between its zinc finger motifs and importin alpha. Moreover, the nuclear localization of PsLSD1 suggests that LSD1 may function as a transcription regulator involved in negatively regulating PCD.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000292929500042&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Multidisciplinary SciencesSCI(E)PubMed11ARTICLE7e22131